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2016, Number 3

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Rev Mex Pediatr 2016; 83 (3)

Morquio syndrome: new heterozygous mutation of the GALNS gene in two siblings from south-west Colombia. Clinical, molecular, and bioinformatic analysis

Pachajoa H, Ruiz-Botero F, Hernández-Amariz MF, Eichler S, Castillo-Giraldo AO

Language: Spanish
References: 22
Page: 85-92
PDF size: 830.75 Kb.


ABSTRACT

Introduction: Mucopolysaccharidosis type IV A, or Morquio syndrome, is an autosomal recessive lysosomal storage disorder that is caused by mutations on the GALNS gene, resulting in the accumulation of keratan sulfate and condroitin sulfate in certain tissues. It is expressed as generalized skeletal dysplasia including short stature, Pectus carinatum, platyspondylia, odontoid hypoplasia, kyphoscoliosis, and genu valgum. Material and methods: 9 and 6 six year old brothers with clinical characteristic of severe Morquio syndrome. GALNS gene sequencing is performed detecting two mutations in both brothers, the first one in exon 3 (c.280C›T p.R94C), and a new mutation in exon 9 (c.998G›A p.G333D), which was determined as potentially pathological. Bioinformatic analysis of the mutations via an in silico analysis of multiple sequence homology, using the Softwares SIFT, PolyPhen, nsSNPAnalyzer, I-Mutant, FOLD X, and DeepView-Swiss-PdbViewer. Discussion: The analyzes showed that the aminoacid changes caused by the presence of these SNPs in the protein could affect its three dimensional structure and its operation, evidencing negative effects in relation to the protein stability, solvent accessibility and polarity which makes them strong candidates to be denominated risk markers for this disease.


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